a) Field of the Invention
This invention relates to morpholinoalkylindenes, which are useful in the treatment of glaucoma, pharmaceutical compositions containing compounds of the invention and methods for use thereof in treating glaucoma.
b) Information Disclosure Statement
Shen U.S. Pat. No. 3,532,752, issued Oct. 6, 1970 discloses 1-alkylidene-3-indenyl aliphatic amines of the general formula ##STR2## wherein
R.sub.1 and R.sub.2, which may be the same or different, are each hydrogen or an alkyl, aryl or aralkyl radical, preferably lower-alkyl, aryl or ar-lower-alkyl containing functional substituents such as hydroxy halo, lower-alkylthio, lower-alkyl, trifluoromethyl, lower-alkylsulfamyl, lower-alkoxy, di(lower-alkyl)sulfamyl, nitro, phenyl and the like;
R.sub.3 is hydrogen, halogen, hydroxy or a lower-alkyl, aryl, ar-lower-alkyl, lower-alkoxy, halo lower-alkyl, lower-alkylthio, arylthio, lower-alkenyl or lower alkoxyphenyl radical;
R.sub.4 and R.sub.5, which may be the same or different, are each hydrogen, lower-alkyl, halo lower-alkyl, lower-alkoxy lower-alkyl, hydroxy lower-alkyl, lower-alkenyl, lower-alkynyl, cyclopropyl lower-alkyl, tetrahydrofurfuryl, cyclic lower-alkyl, or together with the nitrogen to which they are attached, morpholino, piperidino, piperazino, substituted piperazino such as N-phenylpiperazino, N-hydroxyethylpiperazino and N-methylpiperazino, pyrrolidino and 1,2,5,6-tetrahydropyridino radicals;
R.sub.6 is hydrogen, halogen, lower-alkyl, lower-alkoxy, alkylthio, aryl, aryloxy or trifluoromethyl and together with R.sub.7 when they are ortho to each other lower-alkyenedioxy;
R.sub.7 is hydrogen, hydroxy, lower-alkyl, lower-alkoxy, nitro, amino, lower-alkylamino, di(lower-alkyl)amino, loweralkanoylamino, lower-alkanoyl, bis(hydroxy lower-alkyl)amino, 1-pyrrolidino, 4-methyl-1-piperazinyl, 4-morpholinyl, alkylsulfonyl, cyano, trifluoromethyl halogen, di(loweralkyl)sulfamyl, benzylthio, benzyloxy, lower-alkylbenzyloxy, lower-alkoxybenzyloxy, halogenbenzyloxy, lower-alkenyl, loweralkenyloxy, 1-azacyclopropyl, cyclopropyl lowered alkoxy, cyclobutyl lower alkoxy and together with R.sub.6 when they are ortho to each other, lower alklenedioxy;
R.sub.8 is one of the following groups: ##STR3## in which R.sub.9 and R.sub.10, which may be same or different, are each hydrogen, lower-alkyl, halo lower-alkyl, benzyloxy lower-alkyl, hydroxy lower-alkyl, lower-alkenyl, phenyl or lower-alkynl. The compounds are stated to be useful as antiinflammatory and antipyretic agents.
Shen et al. U.S. Pat. No. 3,622,623 , issued Nov. 23, 1971 discloses ##STR4## in which R.sub.1 may be aryl or heteroaryl;
X may be alkylene or alkenylene; PA1 R.sub.2 may be hydrogen, alkyl, aralkyl, aryl, heteroaryl, halogen, hydroxy, alkoxy, haloalkyl, alklthio, and arylthio; PA1 5,6-dimethylindene PA1 2-methy1,5,6-fluoro,6-chloroindene PA1 6-trifluoromethylindene PA1 2-ethyl-5,6-dimethoxyindene PA1 5-hydroxy-6-methylindene
R.sub.3 may be hydrogen, lower-alkyl, halo lower-alkyl, fluorine, amino acylamino, dialkylamino, N-morpholino, alkenyl, aralkylthio, hydroxy and alkoxy and together with R.sub.3 ' a methylene;
R.sub.4, R.sub.5 and R.sub.6 each may be hydrogen, alkyl, alkoxy, nitro, amino, acylamino, alkylamino, dialkylamino, dialkylaminoalkyl, sulfamyl, alkylthio, mercapto, alkyl-sulfonyl, arylsulfonyl, halogen, cyano, carboxyl, carbalkoxy, carbamido, aryl, halogenoalkyl, alkenoxy, aryloxy, alkenyl, aryloxy, cycloalkyl and cycloalkyloxy, and
M may be hydroxy, lower-alkoxy, substituted lower-alkoxy, amino, alkylamino, dialkylamino, N-morpholino, hydroxyalkylamino, polyhydroxyalkylamino, dialkylaminoalkylamino, aminoalkylamino, and the group OMe in which Me is a cation as well as the 2,3-dihydro derivatives of said compounds. These compounds are stated to be useful as analgesics, anti-inflammatory and antipyretic agents.
Shen et al. U.S. Pat. No. 3,654,349, issued Apr. 4, 1972 discloses compounds of the formula ##STR5## wherein
Ar may be aryl or hetaryl;
R.sub.1 may be hydrogen, lower-alkyl or halogenated lower-alkyl;
R.sub.2 may be hydrogen or alkyl;
R.sub.3, R.sub.4, R.sub.5 and R.sub.6 each may be hydrogen, alkyl, aclyoxy, alkoxy, nitro, amino, acylamino, alkylamino, dialkylamino, dialkylaminoalkyl, sulfamyl, alkythio, mercapto, hydroxy, hydroxyalkyl, alkylsulfonyl, halogen, cyano, carboxyl, carbalkoxy, carbamido, halogenoalkyl, cycloalkyl or cycloalkoxy;
R.sub.7 may be alkylsulfinyl or alkylsulfonyl;
R.sub.8 may be hydrogen, halogen, hydroxy, alkoxy, or haloalkyl; and
M may be hydroxy, lower-alkoxy, substituted lower-alkoxy, amino, alkylamino, dialkylamino, N-morpholino, hydroxyalkylamino, polyhydroxyalkylamino, dialkylaminoalkylamino, aminoalkylamino, and the group OMe, in which Me is a cation.
The compounds are stated to have antiinflammatory, antipyretic and analgesic activity.
Hauck et al. U.S. Pat. No. 4,044,040, issued Aug. 27, 1977, discloses 1-[3-(3-indenyl)propyl]morpholine as an intermediate in the preparation of 4,7-dihydroindenylalkanols and their analogues, stated to be useful in the treatment of hypertension.